Doctoral Dissertation Improvement Award: Effect of Nutrition on Ovarian Aging

华盛顿大学的Baishakhi Basu将进行一项研究，旨在阐明早期和晚期营养不良影响孟加拉国妇女卵巢老化和更年期的机制。大量证据表明，资源贫乏地区的妇女绝经年龄比资源丰富地区的妇女绝经年龄早6个月，这启发了这项研究。造成这种差异的潜在生物学原因尚不清楚。该研究的一个组成部分将调查胎儿和儿童时期的营养压力如何影响月经周期，从而导致更年期。该研究的另一个组成部分将调查晚年的营养压力是否会降低更年期发生的年龄。这项研究的更广泛的影响将是阐明早期营养和后期营养压力影响女性生殖生物学和功能的机制。这项研究将有可能确定哪些生物机制会缩短营养压力下女性的生殖寿命。这项研究有两个不同的组成部分。第一项研究探讨了胎儿生命和儿童营养可能影响卵巢衰老过程的途径。在过渡到更年期，卵巢卵泡池的近枯竭反映在越来越不规则的月经周期。本研究假设，生命早期的营养不良会导致在胎儿时期建立的卵巢卵泡池较小和/或加速卵泡池减少的速度。任何一种影响都会导致卵巢卵泡池更早的耗尽，从而更早地过渡到更年期。这项研究将利用之前收集的2300名孟加拉国农村妇女的月经日历，这些妇女在1974年严重饥荒之前、期间和之后出生。这些女性出生的家庭参加了1974年的一项社会经济调查，因此，通过检验1974年家庭财富与女性开始过渡到更年期的年龄之间的统计关联，可以检验这一假设。第二个部分检查女性是否经历了一种与压力相关的闭经（没有月经周期），这种闭经会在卵巢卵泡完全耗尽之前扰乱月经周期（真正的更年期）。这种所谓的下丘脑闭经与真正的更年期难以区分，因此可能被误认为是真正的更年期。为了验证这一想法，巴苏将进行为期两个月的调查，其中包括500名在过去9-15个月内停止骑自行车的孟加拉国农村妇女。参与者提供的尿液样本将进行激素标记测试，以区分真正的更年期和下丘脑闭经。

Baishakhi Basu of the University of Washington will conduct research that aims to clarify the mechanisms by which early life and late life undernutrition affects ovarian aging and menopause in Bangladeshi women. The study is inspired by the abundant evidence that the age at which women in resource-poor settings experience menopause is about 6 months earlier than what is found in resource-abundant settings. The underlying biological cause of this discrepancy is unknown. One component of the study will investigate how nutritional stress in fetal life and childhood affects menstrual cycles during the transition that leads to menopause. Another component of the research will investigate whether nutritional stress later in life decreases the age at which menopause occurs. The broader impact of this study will be to elucidate the mechanisms by which nutrition in early life and nutritional stress in later life affects the reproductive biology and function in women. The study will potentially identify which biological mechanisms shorten the reproductive lifespan for women under nutritional stress.The research has two distinct components. The first examines pathways through which fetal life and childhood nutrition may affect the process of ovarian aging. During the transition to menopause, the near depletion of the ovarian follicle pool is reflected by increasingly irregular menstrual cycles. This study hypothesizes that undernutrition during early-life leads to a smaller ovarian follicle pool established in fetal life and/or accelerates the rate at which the follicle pool is reduced. Either effect would result in an earlier depletion of the pool of ovarian follicles and, consequently, an earlier transition to menopause. The research will utilize previously collected menstrual calendars on 2,300 rural Bangladeshi women born before, during and after a severe famine in 1974. The women were born in households that participated in a 1974 socio-economic survey, so the hypothesis is examined by testing for any statistical associations between household wealth in 1974 and the age a woman starts transitioning to menopause. The second component examines whether women experience a type of stress-related amenorrhea (absence of menstrual cycles) that disrupts menstrual cycles before the pool of ovarian follicles is fully depleted (true menopause). This so-called hypothalamic amenorrhea is indistinguishable from, and therefore can be mistaken with, true menopause. To test this idea, Basu will conduct a two month long investigation with the participation of 500 rural Bangladeshi women who have stopped cycling in the past 9-15 months. Urinary specimens provided by the participants will be tested for a hormonal marker that distinguishes true menopause from hypothalamic amenorrhea.